Objective To explore the potential relationship between ubiquitination of transforming growth factor kinase 1(TAK1)/nuclear factor-κB(NF-κB)signaling pathway mediated by ring finger protein 99(RNF99)and septic acute respiratory distress syndrome(ARDS).Methods Plasmid and siRNA transfection were conducted to overexpress or knock down RNF99 in MLE12,and expressions of p65 phosphate and p65 protein were analyzed.The protein interaction between RNF99 and TRAF6 or TAK1 was analyzed by immunoprecipitation assay.Forty mice were randomly divided into WT plus PBS,WT plus LPS,RNF99 specific expression(TG)plus PBS,and TG plus LPS groups,with 10 mice in each group.Sepsis was induced by intraperitoneal injection of 30 mg/kg LPS.Results As compared with vector group,protein expression levels of TRAF6 and TAK1 in MLE12 cells decreased significantly in RNF99 group(P<0.05).Ubiquitinated TRAF6 protein increased in MLE12 cells with RNF99 knockdown.As compared with LPS plus vector group,phosphorylation level of p65 in MLE12 cells was signifi-cantly lower in LPS plus RNF99 group(P<0.05).As compared with si-NC group,protein expression levels of RNF99 and IκBα in si-RNF99 group decreased significantly(P<0.05).As compared with LPS plus si-NC group,phosphorylation level of p65 in LPS plus si-RNF99 group increased significantly(P<0.05).The staining percentage of CD68 macrophages in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Phosphorylation level of p65 in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Conclusion RNF99 regulates NF-κB signaling pathway by interacting with the key regulator of NF-κB signaling pathway(TRAF6/TAK1),and improves lung injury after intraperitoneal injection of LPS in mice.

Transketolase(TKT)is an important enzyme that catalyzes the non-oxidative phase group transfer reac-tion of pentose phosphate pathway(PPP),and is involved in the metabolism of various energy substances in the body,such as glucose,ribose,nucleotides and lipids.TKT can reduce oxidative stress,inflammation,atheroscle-rosis,endothelial dysfunction and Tau protein phosphorylation by inhibiting advanced glycated end-produces(AGEs)produced by non-enzymatic glycosylation(NEG)of proteins and lipids in a high-glucose environment im-proving blood glucose,glucose tolerance and β cell function so to prevent and treat diabetes and its complications.This article reviews research progress on the mechanism of TKT in the treatment of diabetes mellitus and its compli-cations.

[Objective]To analyse the academic characteristics of Jiudetang Yi'an by the famed Qing Dynasty physician LI Yongcui,so as to braoden the schemes of the clinical diagnosis and treatment.[Methods]Using the 67 medical cases recorded in the Jiudetang Yi'an as the primary research subjects,this paper extracted and analyzed the main symptoms,disease locations,syndrome types,treatment principles and prescriptions from these cases.Additionally,this paper referenced other relevant classical texts to summarize LI's academic thoughts and clinical experiences.[Results]LI inherited family medical teachings from a young age and extensively absorbed the essence of various schools of thought,supplementing areas unexplored by his predecessors.Academically,he was grounded in the Huangdi Neijing and was profoundly influenced by Dongyuan's theories,developing unique insights into"Yin fire".In clinical practice,LI strictly adhered to holistic principles,selecting medications based on timing;treating upper body ailments by addressing lower body issues with skillful differentiation;advocating spleen regulation as fundamental while emphasizing the liver harmony and protecting the spleen and kidney functions.LI prioritized complexion and pulse diagnosis,excelling particularly in pulse diagnosis,and basing treatments on pulse-symptom discrepancies.His approach favored mild medications,cautiously employing aggressive treatments,effectively utilizing channel-guiding and envoy drugs,and skillfully incorporating hematite in prescriptions.[Conclusion]Jiudetang Yi'an presents a collection of meticulously selected cases,comprehensive in theory,methodology,prescription,and medication.The distinctive diagnostic and therapeutic features of LI's practice,as encapsulated in these records,offer valuable insights for expanding syndrome differentiation thinking and guiding clinical diagnosis and treatment.This work merits in-depth study and inheritance by future generations of practitioners.

Objective To quantify the setup errors for the different anatomical sites of patients who received intensity-modulated radiotherapy (IMRT) with linear accelerator on-board kilovolt fan beam CT(kV-FBCT) as non-isocenter IGRT and megavolt cone beam CT (MV-CBCT) as isocenter IGRT. Methods A retrospective analysis was performedon 70 patients who underwent radiotherapy, kV-FBCT, and/or MV-CBCT scans after each routine setup prior to IMRT. The average displacement (M), systematic error (Σ), and random error (б) at different treatment sites in the left-right, anterior-posterior, and cranial-caudal directions were calculated according to the individual displacements. The formula 2.5Σ+0.7б was used to estimate the PTV margin in respective direction. For each single patient, the root mean square in three directions was used as 3D displacement. Results A total of 1130 displacements were recorded in the 70 patients. The PTV margin was estimated to be 1.9-3.1 mm in head and neck cancer, 2.8-5.1 mm in thoracic cancer, 4.6-5.1 mm in breast cancer, 3.0-5.5 mm in upper abdominal cancer, and 3.5-6.8 mm in pelvic tumor. For the 3D mean displacements, the head and neck, thoracic, breast, upper abdominal, and pelvic cancer were 2.4±1.0, 4.0±1.6, 4.1±2.0, 4.6±2.1, and 4.6±2.1 mm, respectively. The average 3D displacement obtained by kV-FBCT and MV-CBCT were 4.1 and 3.4 mm, respectively (P=0.212). Conclusion The quantitative setup-error data can be obtained using linear accelerator on-board FBCT, and the non-isocenter IGRT induced set-up error cannot be negligible.

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

Objective:To report a rare case of renal injury secondary to Strongyloides stercoralis infection, and investigate common pathological subtypes, pathogenesis and differential diagnosis of Strongyloides stercoralis infection-associated renal injury combined with literature. Methods:The pathological features of renal biopsy were analyzed by immunofloruscence, light microscope and electronic microscope. The pathological changes of digestive tract and pathogen morphology were observed through endoscope and digestive tract biopsy. The correlation between clinical-pathological features and pathological changes of kidney and digestive tract was analized.Results:The 26-year-old male patient presented with nephrotic syndrome. The pathological changes of renal biopsy were consistent with minimal change disease with interstitial focal eosinophil infiltration. Laboratory examination showed that the patient had unexplained eosinophilia and increased IgE level. Hence the patient was treated with glucocorticoid. After 2 months of therapy, proteinuria decreased and turned to negative while the patient developed progressive headache, gastrointestinal bleeding and progressive decrease of hemoglobin. Emergency gastroscopy showed extensive congestion and erosion of the stomach and duodenum. Gastric mucosal biopsy showed a large number of slender "s" shape larvae in the mucosa. The patient also had bilateral lung infection, positive Escherichia coli in cerebrospinal fluid and purplish skin rash around the umbilicus. A serious infection of Strongyloides stercoralis was diagnosed. After antibiotics and anthelmintic treatment, gastrointestinal symptoms and headache disappeared, and no parasite was found in endoscopy. No recurrence of nephrotic syndrome was found during 2 years of follow-up. Conclusions:Strongyloides stercoralis infection might first present with nephrotic syndrome with handful hints of digestive tract combined with eosinophilia and increased IgE levels. Therefore, in epidemic areas or patients with suspicious exposure history, it is necessary to exclude Strongyloides stercoralis infection before immunosuppressive therapy to avoid fatal complications.

Objective To analyze the therapeutic effect and tolerability of decitabine monotherapy or combined with arsenic trioxide for the treatment of patients with myelodysplastic syndromes (MDS). Methods Clinical characteristics of 32 patients with primary MDS in North Hospital of Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University from January 2014 to April 2017 were retrospectively analyzed. The clinical data of these patients were collected, and the patients were followed up. Decitabine combined with arsenic trioxide was used in 23 cases, decitabine (20 mg·m-·2d-1) and arsenic trioxide (0.16 mg/kg) were administrated from day 1 to day 5 and was repeated every 4-6 weeks. For the remaining 9 cases, only decitabine was applied, decitabine(20 mg·m-2·d-1) was administrated from day 1 to day 5 and was repeated every 4-6 weeks. The clinicopathological characteristics and the effect of genetic mutations on the efficacy of treatment were investigated. Results Of the 32 patients with primary MDS, 18 were male and 14 were female. The patients were 17-72 years old with a median age of 56 years old. Genetic analysis revealed 10 cases with TP53 mutations, 8 cases with TET2 mutations, 4 cases with U2AF1 mutations, 3 cases with RUNX1 mutations, 3 cases with ASXL1 mutations, 2 cases with NRAS mutations, 2 cases with DNMT3A mutations and 1 case with JAK2 V617 mutation. The follow﹣up time was 2-23 months with a median follow﹣up time of 8 months. A total of 21 cases (65.6%) attained treatment response. Among them, there were 10 cases (31.3%) with complete remission (CR), 5 cases (15.6%) with bone marrow complete remission (MCR), and 6 cases (18.7%) with hematological improvement. There was no significant difference in the efficiency and CR rate between the combination group and the monotherapy group (P＝0.441, P＝0.681). Ten cases were found to have TP53 mutations, of which 7 cases had CR. Multivariate analysis demonstrated that TP53 mutation was an independent risk factor for CR (P＝ 0.037). All patients developed myelosuppression after treatment, of which 16 cases developed pulmonary infection. Conclusions Decitabine combined with arsenic trioxide in the treatment of MDS is effective and well tolerated. The therapeutic effects of decitabine monotherapy or decitabine combined with arsenic trioxide for treatment of patients with TP53 mutations are better than the average levels.

From December 2016 to February 2018,5 patients with type Ⅲ or mass type cesarean scar pregnancy (CSP) were treated in Zhejiang Taizhou Hospital.The clinical features,imaging findings and disease outcome were retrospectively analyzed.There were 3 cases of type Ⅲ and 2 cases of mass type,which were diagnosed by transvaginal ultrasound.The CSPs were resected with combination of laparoscopy and hysteroscopy,the average intraoperative blood loss was 80 ml (50-100 ml) and there were not postoperative complications.The average length of hospital stay was 9.4 days (8-12 d).Postoperative serum β-hCG returned to normal in average 22 days (14-30 d),and the menstruation recovered in 22-39 days after operation.The data indicates that resection of type Ⅲ or mass type caesarean scar pregnancy with a combination of laparoscopy and hysteroscopy is an effective treatment.

Objective: Non-suicidal self-injury (NSSI) in adolescents appeared prevalent and multifactorial. This study was to examine the associations between exposure to suicidal behaviors and NSSI in the Chinese adolescents. Methods: Participants included for analyses were 5 154 adolescent students who participated in the baseline survey in 2015 and the first follow-up survey in 2016 of the Shandong Adolescent Behavior and Health Cohort, but with no history of NSSI at the baseline survey. A self-administered structured questionnaire was used to collect data on demographics, behavioral and emotional problems, lifetime and last-year NSSI. Data on the history of exposure to suicide attempt or death of a family member, friend, or close acquaintance were also collected. Multivariate logistic regression methods were used to examine the associations between exposure to suicidal behaviors and NSSI. Results: In the baseline survey, mean age of the 5 154 participants was (14.49±1.48) years, with 48.5% of the participants as girls. Of the participants, 9.0% reported having been exposed to suicidal behaviors, including 6.0% reported to suicide attempt, 4.9% to suicide death, 7.3% to suicidal behaviors of friends/close acquaintances, and 3.1% to suicidal behaviors of relatives. The prevalence rates of NSSI in the last year were significantly higher in adolescents who had been exposed to suicidal behaviors than those who had not (P<0.05). Results from the multivariate logistic regressions showed that exposure to suicide death (OR=1.91, 95%CI: 1.22-3.01) or to suicidal behaviors of relatives (OR=1.79, 95%CI: 1.02-3.12) were both significantly associated with the increased risk of NSSI. Conclusions Experiences related to exposure to suicide-death or suicidal behaviors of relatives were associated with increased risk of NSSI in adolescents. After the suicide events, psychological counseling and health education programs set for high-risk groups were helpful in promoting physical and mental health and preventing the attempt of self-injury in teenagers.

AIM:To analyze the mechanism of tumor-associated macrophage (TAMs) in the development of cervical cancer and to investigate its correlation with Th1/Th2 and Th17/CD4+ CD25+ Foxp3 + Treg.METHODS:Twenty seven cases of cervical cancer and 53 cases of cervical intraepithelial neoplasias (including 22 cases of CIN Ⅱ and 31 cases of CIN Ⅲ) were selected as subjects.The venous blood of patients before treatment was extracted to detect Th1/Th2 and Th17/CD4 + CD25 + Foxp3 + Treg with flow cytometry,and detect serum IFN-γ,IL-4,IL-17A,IL-17F,TGF-β1 and IL-10 levels with ELISA Kits.Furthermore,pathological tissues were extracted during operation,and its TAMsCD68 expression was detected by immunohistochemistry technique.RESULTS:The Th1/Th2 and Th17/CD4 + CD25 + Foxp3 + Treg of cervical cancer were both lower than those of CIN Ⅲ,and those of CIN Ⅲ were both lower than CIN Ⅱ,the difference between groups had statistical significance (P ＜ 0.05).The serum IFN-γ,IL-4,IL-17A,IL-17F,TGF-β1 and IL-10 levels of cervical cancer were all higher than those of CIN Ⅲ,and those of CIN Ⅲ were all higher than CIN Ⅱ,the difference between groups had statistical significance (P ＜ 0.05).The TAMsCD68 expression level of cervical cancer was higher than that of CIN Ⅲ,and that of CIN Ⅲ was lower than CIN Ⅱ,the difference between groups had statistical significance (P ＜ 0.05).The correlation analysis results showed TAMsCD68 expression level had negative correlations with Th1/Th2,Th17/CD4+CD25+ Foxp3+ Treg,and serum IL-17A level,whereas presented positive correlations with serum IL-10 and IL-4 level (P ＜ 0.05).CONCLUSION:TAMs is closely related with Th1/Th2 and Th17/CD4 + CD25 + Foxp3 + Treg in cervical cancer,and possibly is mediating the occurrence and development of cervical cancer through influencing the balance of these two systems.